EEG as predictor for depressive and pain complaints.

The basic goal of the present research project is to carry out a prospective
study within the general population, focusing on the predictability of two
outcome parameters: 1) a change in pain complaints, 2) a change in depressive
symptoms. As such, the present study may lead to a better and more fundamental
insight into etiology, maintenance and recovery mechanism of these two
health-related outcomes.

In this study we are interested in two types of complaints: depressive
complaints (like sadness, loss of interest etc.) and pain complaints. The
choice of these two problem areas is based on the fact that they are both
highly prevalent. In the Netherlands it is estimated that the one-year
prevalence of depression within adults (18-65 years) is 5.8 percent . However,
sub-threshold depressive symptom are much more common. Similarly, chronic
*benign* pain complaints (pain that exists for more than 3 months, which cannot
be sufficiently explained from underlying physical pathology) are observed in
18 percent of the general population. This estimate will even be larger in case
also acute and subacute pain complaints will be included. Because of the high
prevalence of depressive and pain complaints in the general population it is
the intention to use a random selection of subjects from the population of
Maastricht. We expect that we will observe at both measurement moments:
1. Pain complaints (acute, intermittent, chronic): plm. > 18%.
2. Depressive complaints: plm. 5-10%.
3. All remaining subjects will be classified as *healthy*, i.e. without actual
pain and / or depressive complaints.
Finally, we expect that in a number of subjects the health-status will be
changed from t=0 to t=6 months (see below).

Both outcome measures, being pain and depressive complaints will be measured
with questionnaires (with good psychometric properties). From clinical practice
it is known that these two complaints are often associated with each other. One
of the interesting secondary research questions is whether these interrelated
clinical problems demonstrate different EEG activity.

Finally, note that we do not classify subjects with a DSM-IV-diagnosis such as
major depression or with the IASP classification *chronic benign pain*. We are
interested in a change of a continuous symptom score, unlike a change in a
traditional dichotomy 'ill-healthy'.

The rational of this research project will be illustrated by the following
example applied to depressive symptoms. Within a given period of time (in our
study 6 months) four possible courses in the level of (sub-threshold)
depressive symptoms can be envisaged.
First, as will occur in most cases, there is an unchanged, stable situation of
complaints. Second, people can experience a (meaningful) increase in
complaints. Third, a decrease of complaints may also be observed. Fourth people
without complaints can be remain free of complaints. An increase (as measured,
for with the depression score on a questionnaire) may give an indication that
an etiological or augmenting mechanism is active. On the other hand, a
decreasing score may be indicative of an ongoing recovery. An unchanged score
is interesting in two ways. First, starting from a point with already existing
complaints, the unchanged score may be indicative of a symptom-maintaining
mechanism (e.g. an operant reinforcement mechanism). In the case of a
symptom-free start, it may give information that a symptom-free state is being
continued (e.g. active resilience mechanisms).

Embedding in current research lines and theoretical background.
There are two reasons why the present study focuses on these two health
problems. First, as already mentioned above, the prevalence of these health
problems is relatively high. The second argument is based on the fact that the
department of Psychiatry and Neuropsychology (MUMC) has experimental as well as
clinical experience in these two health problems. With respect to pain, a
recent dissertation has been completed by Vossen. The results of this
dissertation show the importance of objective EEG / ERP measures in pain
assessment. In addition, the hypothesized predictive link between pain measures
in a laboratory setting and pain ratings in the home setting could be
demonstrated. Furthermore, it was demonstrated that depressive patients with
chronic back pain showed less to no habituation to experimental pain stimuli,
thus demonstrating the importance of a diminished habituation as a mechanism in
the etiology / maintenance of chronic pain. In addition, a large body of
literature exists emphasizing the relationship between complaints (such as
pain, depression) and personality factors. The influence of factors such as
neuroticism and extraversion /introversion have been demonstrated both
experimentally as well as
clinically. Vossen concluded, that longitudinal studies are needed to get more
insight in the aetiology and chronification of pain complaints and the
influence of personality and psychological problems.

Over the last decade, several articles and dissertations have been completed at
the department of Psychiatry (MUMC) within the related fields of depression and
the influence of genetics. These research projects demonstrate the
multidimensional (etiological) nature of depression. In many of these studies,
questionnaires are used to assess depression. However it is known that this
(questionnaire) data is prone to several forms of bias. The conclusions of
these research projects are that future studies should incorporate more
objective measures, such as EEG / ERP, EMG and ECG, in addition to
questionnaires. Objective measures improve the quality of clinical (diagnostic
and effect) assessment.


As stated above, at t = 0 and at t = 6 months four so-called *vulnerability
experiments* are carried out. Based on findings in literature four
mini-experiments are carried out to get specific insight into crucial factors
in the etiological / maintaining mechanisms of both pain and depressive
complaints.
1. EEG-experiments investigating attentional bias towards pain and emotional
queued words. In a recent review, the significance of attentional bias towards
pain as a risk factor in the process of chronification was demonstrated. It is
therefore proposed to demonstrate how in a general population sample,
attentional bias towards pain and depression related words is associated with
cortical activity, as measured with EEG / ERP.
2. A large body of literature exists, showing the relationship between abnormal
stress reactivity (measured as muscle-reactivity and heart rate) and the
development of chronic pain. Rehabilitation centre *t Roessingh in Enschede in
the Netherlands has extensive experience in performing such experiments.
3. As already mentioned above, a dissertation project carried out at Maastricht
University demonstrated the importance of abnormal habituation as a possible
mechanism in the chronification process of pain.
4. Mood reactivity can be experimentally manipulated by so called *mood
inductions*. An example would be looking at pictures or movies with different
emotional content. Especially in research concerning depression, the degree of
reactivity seems to be a significant *vulnerability* parameter. Because of the
strong relationship between pain and depression, abnormal mood reactivity may
be an important shared factor in the development of pain and depression.

In sum, this study focuses on predicting changes in two psychopathological
measures (the dependent variables) with changes in cortical reactivity
associated with experimental induction of these same psychopathological
measures (being the independent / predictor variables). The results of the 4
experimental inductions may provide much better causal evidence linking
specific cortical reactivity to specific symptoms and changes within these.
*

Primary Objective:
1. An explorative study to investigate whether a change in
pain complaints or depressive symptoms can be predicted using baseline EEG/ERP
measures derived from vulnerability experiments.

Secondary Objective(s):
1. To explore changes in cortical processing (in response to the four
vulnerability experiments) in relation to the etiological, maintaining and
recovery mechanisms of pain and depressive complaints.
2. To compare the EEG/ERP t0 and t6 months results with those from a breast
cancer surgery population (nl34275.068.11) with respect to the development of
pain and depressive complaints.
3. Since only siblings will be included, analyses concerning the (possible)
influence of a familial component in the EEG responses will be carried out.

A prospective cohort study with two moments of assessments:
1. baseline t=0
2. follow-up 1 at 6 months

Assessments 1 and 2 consist of an psychophysiological (EEG, ECG, EMG)
registration while performing the four vulnerability tasks, as well as the
administration of several health-related and personality questionnaires.

There is no benefit for subjects participating in the study. A financial (50¤)
reward will be given. There are no risks involved. We estimate the burden for
the patient as light to moderate because of the following two factors:
1. Two EEG measurements (of 3,5 hours each), take place at the university.
2. The completion of several pain- and health related questionnaires, including
a personality questionnaire (NEO).